The alpha-ketoglutarate dehydrogenase complex is a multi-enzyme system which after purification shows little or no tendency to be affected by mitochondrial metabolites, whereas, in the intact mitochondria or in crude extracts both regulation by GTP or succinyl-CoA and involvement in other DPN-linked processes have been reported. The object of this proposed research is to elucidate the mechanism by which the oxidation of alpha-ketoglutarate is regulated in heart, kidney, and liver mitochondria. In addition, the involvement of any one of the components of the complex with other mitochondrial reactions will be investigated. The components of the complex will be isolated by various techniques and compared from the different tissue sources. Specific antibodies to each will be prepared and an immunochemical approach will be used to elucidate differences in components of the complexes and also component involvement in other reactions in crude mitochondrial suspensions. This investigation will include the complete characterization of heart, kidney, and liver complexes and components with respect to structure, function and regulation. This study will also characterize further the inhibition specific for mammalian KGDC which has been observed by this Investigator as well as the related reactivation.